Acquired resistance of chronic lymphocytic leukemia (CLL) to chemotherapy is an important clinical problem and is often caused by cytogenetic aberrations or gene mutations affecting the ATM-p53 DNA damage response pathway or other pathways. However, there are also a lot of resistant cases without detectable mutations and we decided to check whether there are specific epigenetic changes at the level of DNA methylation that might underlie resistance development in CLL. We used Illumina Infinium HumanMethylation450 BeadChips to obtain DNA methylation profiles of 71 CLL patients with different responses to chemotherapy. Fifty-one patients were subjects of the CLL2O clinical trial and 36 of them were categorized as relapsed/refractory after treatment with fludarabine- or bendamustine-containing regimens, whereas the other 15 patients as well as 20 additional patients not on the trial were untreated at the time of sampling. Although we could not correlate chemoresistance with epigenetic changes, we believe that the dataset is valuable and can be used by researchers to test other hypotheses, especially as the patients are well characterized regarding different prognostic and molecular markers (IGHV mutation status, chromosome aberrations, TP53 mutation status, etc.).
Overall design
72 samples of CLL patients were analyzed by Illumina Infinium HumanMethylation450 BeadChips. Two consecutive samples (40 months apart) from one patient were used to confirm reproducibility of the assay, as well as stability of DNA methylation profiles over time. Fifty-one of the patients were subjects of the multi-centre CLL2O clinical trial (clinicaltrials.gov: NCT01392079) and we have subdivided them here in 4 subgroups depending on their del(17p)/TP53mut and treatment/response statuses as follows: groups A (N = 15), B (N = 10) and C (N = 11) consisted of patients with del(17p) and/or TP53 mutation and group E (N = 15) consisted of patients without del(17p) or TP53 mutation. Patients in group A were not treated previously but required treatment, patients in group B had relapsed after treatment with fludarabine- or bendamustine-containing regimens and patients in groups C and E were refractory to fludarabine or bendamustine. Samples from patients in all these groups were taken prior to the start of the CLL2O clinical trial. Additional 20 cases (group D) were patients of the University Hospital in Ulm who did not have del(17p) or TP53 mutation and who were not previously treated.
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